Skin care product and method of use

ABSTRACT

A cosmetic skin care product that includes an applicator and a skin care composition. The applicator includes a uni-directional magnetic array with a pitch of between 1.7 and 2.5 and a magnetic field strength of between about 24.0 and 36.0 mT. The skin care composition includes palmitoyl-lysine-threonine-threonine-lysine-serine and a dermatologically acceptable carrier. The magnetic array is tailored to enhance penetration of the Pal-KTTKS into skin during application of the skin care composition. The applicator may include a second magnetic array juxtaposed on a first magnetic array to form a bi-directional array that enhances penetration of the Pal-KTTKS into skin.

FIELD

The present invention relates generally to skin care products thatprovide enhanced penetration of a skin care active into skin. Morespecifically, the present invention relates to pairing of an applicatorcomprising a magnetic array and a skin care composition including skincare actives that have particular diamagnetic properties.

BACKGROUND

Topical skin care compositions containing actives that provide benefitsto skin are well known. It also known that the skin health andappearance benefits provided by a cosmetic skin care active may beimproved when the active can penetrate deeper into the skin. Forexample, peptides (e.g., di-, tri-, tetra- and pentapeptides) and theirderivatives, which are known for use in regulating a variety of skinconditions, typically need to penetrate skin to provide the desiredbenefit. In one particular example, the peptide derivativepalmitoyl-lysine-threonine-threonine-lysine-serine, also known asPal-KTTKS (SEQ ID NO: 1), is used in skin care compositions to improvethe signs of skin aging. It is believed, without being limited bytheory, that Pal-KTTKS (SEQ ID NO: 1) stimulates collagen production inthe dermal fibroblasts, which are the skin cells primarily responsiblefor collagen production, resulting in a reduction of the appearance offine, lines and wrinkles. However, to reach the dermal fibroblasts, thePal-KTTKS (SEQ ID NO: 1) must penetrate through the epidermal layers ofthe skin. Thus, it would be desirable to find a suitable way to improvethe skin penetration of cosmetic skin care actives such as Pal-KTTKS(SEQ ID NO: 1).

However, effective delivery of skin care actives, such as Pal-KTTKS (SEQID NO: 1), into skin is an ongoing challenge. It is not uncommon forskin care actives to be introduced to skin via topical application of,for example, creams, lotions and essences. However, the actual andperceived benefits of skin care actives such as Pal-KTTKS (SEQ ID NO: 1)are largely dependent on the amount of skin care active that penetratesthe top layer of skin and the depth to which it penetrates. There arevarious factors that limit the amount of active agent that can penetrateskin, and at present there is little control over the positioning andresidency of the active agents following penetration into skin.

The amount of active agent provided in a skin care composition can beincreased in various ways, for example, by increasing the amount ofactive agent in the skin care composition. However, this often leads tocompositions that do not have a good sensory feel, increased formulationchallenges, stability issues and increased manufacturing costs.

One approach to improving the efficacy of a skin care active is to usechemical penetration enhancers to facilitate changes in skinpermeability, allowing enhanced penetration of the skin care active.However, the use of chemical penetration enhancers can be problematicdue to unknown interaction with the active agent and the potential foradverse side effects such as irritation of skin and mucosal surfaces.

Mechanical approaches to increasing skin penetration of actives havealso been explored. For example, one such approach known asiontophoresis utilizes an electrical energy gradient to accelerate acharged active agent(s) across the skin (or other barrier). An exampleof a device that uses iontophoresis is described in U.S. Pat. No.7,137,965. However, iontophoresis is only suitable for specific activeagents with certain ionic structures and can be injurious to certaindermal barriers due to exchange ion degradation. Additionally,iontophoresis requires the use of intimate electrical contact andadhesive electrodes, which are not suitable for all target surfaces orbarriers.

Other techniques for creating mobility and/or direction in the movementof active agent(s) include magnetokinetics and magnetophoresis. However,these techniques have been difficult to implement due to poorperformance, high hardware and energy requirements, and cost. An exampleof a device that utilizes magnetophoresis is described in US2009/0093669. While these methods claim to increase the amount ofpenetration of skin care actives into skin, they still do not provideenhanced penetration in a controlled manner—both in terms of amount ofpenetration and depth of penetration.

In another example of a device design to effectively deliver skin careactives, WO 2011/156869 discloses a method of delivering a skin careagent through a dermal barrier using one or more displaced dipolarmagnetic elements. However, this method still does not provide atargeted approach that takes account of the unique properties andtargeted benefit areas in skin of different skin care actives.

Accordingly, there is a need to provide a cosmetic product that canprovide improved penetration of specific cosmetic actives into skin in acontrolled manner.

SUMMARY

A cosmetic skin care product comprising an applicator and a magneticarray is disclosed herein. The magnetic array comprises a first layer ofone or more dipolar pairs of alternating magnetic poles with a pitch ofbetween 1.7 mm and 2.5 mm and an overall magnetic field strength of thefirst layer of between 24 mT and 30 mT. The skin care compositioncomprises an effective amount of a skin care active with a diamagneticsusceptibility of between about −400 and −600 (e.g., Pal-KTTKS (SEQ IDNO: 1)) and a dermatologically acceptable carrier. In some instances,the present skin care product may include one or more of the followingfeatures in any combination: a magnetic array with a thickness ofbetween 0.8 and 1.2 mm, or about 1.1 mm; a magnetic array with a pitchof between about 1.9 and 2.3 mm, or about 2.1 mm; a magnetic array thatenhances delivery of the Pal-KTTKS (SEQ ID NO: 1) (e.g., at least 1.5×,at least 2.5×, at least 3.5×, at least 4× or even at least 5×) accordingto the Tape Stripping method; a magnetic array that enhances delivery ofthe Pal-KTTKS (SEQ ID NO: 1) as measured in tape strips 2 to 10, tapestrips 4 to 10, tape strips 6 to 10 or even tape strips 8 to 10; amagnetic array that includes a plurality of dipolar magnetic elementsarranged in pairs to form an alternating pattern of magnetic polarities(e.g., a pole of a first dipole pair is adjacent a pole of a seconddipole pair of the same polarity); a magnetic array that comprises aferromagnetic material (e.g., iron, iron containing materials, cobalt,cobalt containing materials, strontium, strontium containing materials,barium, barium containing materials, nickel, nickel containingmaterials, alloys and oxides of these and combinations thereof); amagnetic array that comprises boron, carbon, silicon, phosphorous,aluminum, neodymium and/or samarium; an applicator comprising a coverthat covers a skin facing surface of the applicator; an applicator thatcomprises a cover that has a surface with a dry coefficient of frictionat least 10% less than the skin facing surface of the applicator; anapplicator that comprises a cover that has a surface with a wetcoefficient of friction that is at least 2 times less than the skinfacing surface of the applicator; a magnetic applicator and a skin carecomposition packaged together in a single package; a magnetic applicatorand a skin care composition that are package separately and the separatepackages are joined to one another; a magnetic array comprising about 12poles per 25.4 mm; a first uni-directional magnetic array is juxtaposedon a second uni-directional magnetic array to form a bi-directionalmagnetic array, and the second magnetic array has a pitch and a magneticfield strength that are both less than or equal to the pitch andmagnetic field strength of the first magnetic array (e.g., the secondmagnetic array has a pitch of between 0.8 and 1.3 and a magnetic fieldstrength of between about 1 and 20 mT); a second magnetic array that hasa thickness of between about 0.005 mm and 0.5 mm; and/or a firstmagnetic array angularly offset from a second magnetic array, forexample, by about 90 degrees.

Also disclosed is a method of enhancing the delivery of Pal-KTTKS (SEQID NO: 1) to a target portion of skin in need of treatment, comprising:identifying a target portion of skin in need of treatment; applying askin care composition to the target portion of skin, wherein the skincare composition comprises an effective amount of Pal-KTTKS (SEQ IDNO: 1) and a dermatologically acceptable carrier; and contacting theskin care composition with an applicator comprising one of the magneticarrays disclosed herein above.

The magnetic arrays herein are designed to work in conjunction with thespecific diamagnetic properties of Pal-KTTKS (SEQ ID NO: 1). The overallmagnetic field strength of the magnetic array determines the amount ofrepulsive force induced in the Pal-KTTKS (SEQ ID NO: 1) and, as aconsequence, the depth within skin to which it is driven, while thepitch of the magnetic poles determines the overall profile of themagnetic field. Use of such a magnetic array together with a compositioncontaining Pal-KTTKS (SEQ ID NO: 1) enhances the amount of Pal-KTTKS(SEQ ID NO: 1) that: a) penetrates into a user's skin and b) ispositioned at a layer of skin where it is likely to be most effective.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A to 1D are perspective views of applicators of the skin careproduct described herein.

FIG. 2A shows schematically a typical bar magnet having a north andsouth pole.

FIG. 2B shows schematically a dipolar pair of magnets.

FIGS. 2C and 2D show schematically different arrangements of dipolarpairs in a magnetic array.

FIGS. 3A to 3E illustrate schematically the magnetization andcorresponding magnetic field generated in a magnetic array.

FIGS. 4A and 4B illustrate schematically different ways of constructinga bi-directional magnetic array.

FIG. 4C shows schematically a representation of the magnetic fieldgenerated by a bi-directional array.

FIG. 5 is a plot of the enhanced penetration of Pal-KTTKS (SEQ ID NO: 1)using a magnetic array.

FIG. 6 is a plot of the enhanced penetration of Pal-KTTKS (SEQ ID NO: 1)using a magnetic array.

FIG. 7 is a plot of active versus passive application of Pal-KTTKS (SEQID NO: 1).

FIG. 8 illustrates the test setup for the Coefficient of FrictionMethod.

DETAILED DESCRIPTION Sequence Listing

A sequence listing that sets forth the amino acid sequence for SEQ IDNO: 1 herein is on file as an ASCII text file titled“13538M_seq_list_ST25.” This ASCII text file was created on Apr. 16,2018 and is 4.28 KB in size. In accordance with MPEP § 605.08 and 37 CFR§ 1.52(e), the subject matter in the ASCII text file is incorporatedherein by reference.

The skin care products disclosed herein exploit the unique diamagneticproperty of Pal-KTTKS (SEQ ID NO: 1) to enhance penetration of thisactive into skin. Diamagnetism is the property of an object or materialwhich causes it to create a magnetic field in opposition to anexternally applied magnetic field, thus causing a repulsive effect.Surprisingly, it has been discovered that by pairing a specificallytailored magnetic array with Pal-KTTKS (SEQ ID NO: 1), penetration ofthe active into skin can be enhanced in a controllable way. Utilizingthis discovery, it is possible to provide a cosmetic skin care productin which Pal-KTTKS (SEQ ID NO: 1) and/or other skin care actives aredelivered into skin to the point where they can provide a better skincare benefit than conventional skin care products.

Definitions

“About” when used in the context of a parameter or range means a valuethat is within 30% of the stated value (e.g., with 25%, 20%, 15%, 10%,5%, 2% or even within 1%).

“Apply” or “application,” as used in reference to a composition, meansto apply or spread the composition onto a surface of keratinous tissue.

“Derivative” refers to a molecule similar to that of another one, butdiffering from it in respect of a certain functional moiety. Derivativesmay be formed by known reactive pathways. Suitable functional moietiesinclude esters, ethers, amides, amines, carboxylic acids, hydroxyls,halogens, thiols, and/or salt derivatives of the relevant molecule.Peptide derivatives include peptides joined to another moiety such as afatty acid chain.

“Disposed” refers to an element being located in a particular place orposition relative to another element.

“Joined” means configurations whereby an element is directly secured toanother element by affixing the element directly to the other element,and configurations whereby an element is indirectly secured to anotherelement by affixing the element to intermediate member(s) that in turnare affixed to the other element.

“Keratinous tissue” refers to keratin-containing layers disposed as theoutermost protective covering of mammals which includes, but is notlimited to, skin, hair, nails, cuticles, etc.

“Magnetic field” and “magnetic flux density” are used interchangeablyherein and refer to the vector field measured in teslas.

“Magnetic material” means a material that can be made into a permanentmagnet.

“Permanent magnet” means a magnetic material that has been magnetizedsuch that it produces its own persistent magnetic field without the useof an electrical power source.

“Pole” refers to the portion of a magnet that exhibits a higher magneticflux density than the adjacent regions of the magnet. For example, aconventional bar magnet has 2 poles disposed at opposite ends where themagnetic flux density is highest.

“Regulating skin condition” means improving skin appearance and/or feel,for example, by providing a benefit, such as a smoother appearanceand/or feel. Herein, “improving skin condition” means effecting avisually and/or tactilely perceptible positive change in skin appearanceand feel. The benefit may be a chronic or acute benefit and may includeone or more of the following: reducing the appearance of wrinkles andcoarse deep lines, fine lines, crevices, bumps, and large pores;thickening of keratinous tissue (e.g., building the epidermis and/ordermis and/or sub-dermal layers of the skin, and where applicable thekeratinous layers of the nail and hair shaft, to reduce skin, hair, ornail atrophy); increasing the convolution of the dermal-epidermal border(also known as the rete ridges); preventing loss of skin or hairelasticity, for example, due to loss, damage and/or inactivation offunctional skin elastin, resulting in such conditions as elastosis,sagging, loss of skin or hair recoil from deformation; reduction incellulite; change in coloration to the skin, hair, or nails, forexample, under-eye circles, blotchiness (e.g., uneven red coloration dueto, for example, rosacea), sallowness, discoloration caused byhyperpigmentation, etc.

“Safe and effective amount” means an amount of a compound or compositionsufficient to significantly induce a positive benefit, preferably apositive skin or feel benefit, including independently or incombinations the benefits disclosed herein, but low enough to avoidserious side effects (i.e., to provide a reasonable benefit to riskratio, within the scope of sound judgment of the skilled artisan).

“Signs of skin aging” include, but are not limited to, all outwardvisibly and tactilely perceptible manifestations, as well as any macro-or micro-effects, due to keratinous tissue aging. These signs may resultfrom processes which include, but are not limited to, the development oftextural discontinuities such as wrinkles and coarse deep wrinkles, finelines, skin lines, crevices, bumps, large pores, unevenness orroughness; loss of skin elasticity; discoloration (including undereyecircles); blotchiness; sallowness; hyperpigmented skin regions such asage spots and freckles; keratoses; abnormal differentiation;hyperkeratinization; elastosis; collagen breakdown, and otherhistological changes in the stratum corneum, dermis, epidermis, vascularsystem (e.g., telangiectasia or spider vessels), and underlying tissues(e.g., fat and/or muscle), especially those proximate to the skin.

“Skin” means the outermost protective covering of mammals that iscomposed of cells such as keratinocytes, fibroblasts and melanocytes.Skin includes an outer epidermal layer and an underlying dermal layer.Skin may also include hair and nails as well as other types of cellscommonly associated with skin, such as, for example, myocytes, Merkelcells, Langerhans cells, macrophages, stem cells, sebocytes, nerve cellsand adipocytes.

“Skin care” means regulating and/or improving a skin condition. Somenonlimiting examples include improving skin appearance and/or feel byproviding a smoother, more even appearance and/or feel; increasing thethickness of one or more layers of the skin; improving the elasticity orresiliency of the skin; improving the firmness of the skin; and reducingthe oily, shiny, and/or dull appearance of skin, improving the hydrationstatus or moisturization of the skin, improving the appearance of finelines and/or wrinkles, improving skin exfoliation or desquamation,plumping the skin, improving skin barrier properties, improve skin tone,reducing the appearance of redness or skin blotches, and/or improvingthe brightness, radiancy, or translucency of skin.

“Skin care active” means a compound or combination of compounds that,when applied to skin, provide an acute and/or chronic benefit to skin ora type of cell commonly found therein. Skin care actives may regulateand/or improve skin or its associated cells (e.g., improve skinelasticity; improve skin hydration; improve skin condition; and improvecell metabolism).

“Skin care composition” means a composition that includes a skin careactive and regulates and/or improves skin condition.

“Skin care product” as used herein refers to a product that includes askin care composition. Some nonlimiting examples of “skin care products”include skin creams, moisturizers, lotions, and body washes.

Skin Care Product

The skin care product described herein includes a skin care compositioncontaining one or more skin care actives, one of which is Pal-KTTKS (SEQID NO: 1), and an applicator that includes a magnetic array tailored toenhance delivery of the Pal-KTTKS (SEQ ID NO: 1) into skin. The skincare composition and applicator may be packaged and sold together as asingle product offering and/or they may be packaged separately to besold individually. In some instances, the skin care composition and theapplicator may be packaged in separate packages (e.g., in individualprimary packages), which are then joined to one another or placed in asingle secondary package. It may be desirable to include indicia on theapplicator, the skin care composition and/or their respectivepackage(s), which indicate that the magnetic properties of the array aretailored for use with the skin care composition, for example, to enhancepenetration of one or more skin care actives. Indicia suitable for suchuse are not particularly limited and may include, for example, words,letters, numbers, shapes, colors, pictures and diagrams, whichcommunicate to a consumer that the magnetic array is intended for usewith the corresponding cosmetic composition. In some instances, theindicia may provide a non-verbal communication to a user that themagnetic array enhances penetration of Pal-KTTKS (SEQ ID NO: 1).

Applicator

The cosmetic skin care product described herein includes a suitableapplicator for either applying a skin care composition to a targetportion of skin or placing above and/or contacting a target portion ofskin to which a skin care composition has already been applied. The formof the applicator may vary according to the intended target area ofapplication on skin. For example, if the skin care composition is awhole body cream, then the applicator may be sized and/or shaped toapply the composition to larger surfaces and/or body parts (e.g., thelegs, arms, abdomen and/or back). In some instances, the skin carecomposition may be intended for use in smaller areas such as the face(e.g., cheeks, forehead, chin, nose, and peri-orbital regions). In suchcases, the applicator may be correspondingly shaped and sized to usewith smaller surface areas.

A magnetic array for incorporation into the present applicators may beconfigured to provide a skin contacting surface of the applicator (i.e.,the magnetic array is disposed on the applicator such that it is broughtinto contact with a target skin surface when the applicator is used asintended). Thus, it is important for the magnetic material to be safefor topical use on skin, especially when used with a topical skin carecomposition. It may be desirable to select a magnetic material thatprovides a pleasant feel contacted with skin. For example, the magneticarray may be embedded in the applicator such that the applicator and themagnetic array are a unitary device that provides a smooth, comfortablesurface when contacted with skin.

In some instances, the applicator may include an optional cover placedover at least a portion of the magnetic array and/or skin contactingsurface, such that the cover becomes the skin contacting surface of theapplicator. The cover may be permanently joined to the applicator, orthe cover may be removable, detachable and/or replaceable. It may bedesirable for the cover to have a coefficient of friction that is lessthan that of the magnetic substrate of the magnetic array, which canprovide a more desirable user experience when applying a skin carecomposition with the applicator. In some instances, the cover may have adry coefficient of friction (i.e., a coefficient of friction measuredwithout using a composition) that is between 10 and 50% less than themagnetic substrate (e.g., 15%, 20%, 25%, 30%, 35%, 40%, or even 45%less) according to the Friction Test described in Example 3 below. Whenused to apply a skin care composition, the cover may exhibit acoefficient of friction that is up to 10 times less than the magneticarray (e.g., between 2× and 10× less, 3× and 7× or even between 4× and6× less).

The optional cover, when included, may be formed from a material thatprovides a skin contacting surface with better cooling properties thanthe magnetic substrate. For example, the cover may be formed of amaterial that has a high thermal conductivity of, for example, at least50 W/mK, 100 W/mK or 200 W/mK. Providing a cover with high thermalconductivity feels cool when contacted with skin. Because the thicknessof the cover affects the distance that the magnetic flux density of themagnetic array extends, especially when formed from a non-magneticmaterial, it is important to ensure that the thickness of the cover doesnot undesirably inhibit the strength of the applied magnetic field.Suitable cover thicknesses are between 0.1 mm and 5 mm (e.g., between0.2 and 4 mm, 0.5 and 3 mm, or even between 1 and 2 mm), fornon-magnetic materials.

FIGS. 1A, 1B and 1C and 1D show non-limiting examples of applicators100, 200, 300 and 400, respectively, for use in the present skin careproducts. The applicator 100 shown in FIG. 1A has a substantiallycylindrical base 102 with a skin contact surface 104 extending acrossthe base. A handle 106 extends from the base in a directionsubstantially perpendicular to the skin contact surface. A magneticarray is disposed inside the base (not shown), adjacent to and inparallel with the skin contact surface so that, in use, the magneticarray will be substantially parallel to any surface on which theapplicator is used.

The applicator 200 shown in FIG. 1B has a rounded tip 202 that may besuitable for use around the eye. The rounded tip 202 may be integrallyformed with a handle 204, or it may be formed as a ball held within asocket 206 at the end of the handle 204. A magnetic array (not shown),formed of a flexible substrate is disposed inside the rounded tip 202,such that as the tip 202 is rolled over a surface of skin, the magneticarray will be substantially parallel to the surface of skin. Thus, thetip 202 functions as a cover for the magnetic array disposed within thetip 202.

The applicator 300 shown in FIG. 1C has an elongate handle 302 with askin contacting tip 304 disposed on a skin facing side 306 of theapplicator 300. A magnetic array (not shown) can be disposed inside theapplicator 300, adjacent to and in parallel with the skin contact tip,such that the magnetic array will be substantially parallel to anysurface on which the applicator 300 is used.

The applicator 400 shown in FIG. 1D includes a removable cover 410disposed at one end of the applicator 400 and a handle 402 disposed atthe other end of the applicator 400. The cover 410 is joined to the skinfacing side 404 of the applicator 400 and forms a skin contactingsurface of the applicator 400, when used as intended. The cover 410 maybe removed and/or replaced, as desired. In some instances, the cover 410may be removed and reattached, for example, to facilitate cleaning thecover 410 and/or applicator 400. In some instances, the cover 410 may bedisposable. For example, the cover 410 may be removed and discardedafter one or more uses, but typically less than ten uses, and replacedwith a different cover. The cover 410 may be joined to the applicator400 by any suitable means known in the art.

The applicators herein may be used to directly apply a skin carecomposition, or used to enhance penetration of skin care actives withina skin care composition after application of the skin care compositionby some other means, for example, by finger application. For example,the applicator may be designed for movement across the skin'ssurface—either through manual operation or mechanical means (e.g., avibrating device) or held in position stationary above a target area ofskin to which a skin care composition has been applied. A vibratingdevice may include any mechanism, electrical or mechanical, adapted forreciprocal and/or rotational movement of the magnetic material. Forexample, the magnetic material may be associated with a drive mechanismthat is capable of reciprocal movement.

Alternatively, the applicator may be made in the form of, for example, aleave-on patch, in which case the applicator may be formed of a woven,flexible fabric. The patch may be formed with an adhesive section suchthat it can be adhered to a skin's surface following application of theskin care composition or the skin care composition may be containedwithin the patch.

Magnetic Array

The present applicator includes a magnetic array specifically tailoredto provide improved penetration of Pal-KTTKS (SEQ ID NO: 1). Themagnetic array described herein uses selectively magnetized permanentmagnets to generate a magnetic field. The magnets may be formed of anysuitable ferromagnetic substrates, including, but not limited to: ironor an iron containing material (e.g., a ferrite such as barium ferrite,magnetite, or mild steel), a cobalt material, a strontium material, abarium material, a nickel material, alloys and oxides of these,combinations thereof and the like. In some instances, the magnetic arraysubstrate may include a metalloid component such as boron, carbon,silicon, phosphorous or aluminum. Rare earth material such as neodymiumor samarium may also be used.

In a conventional bar magnet 500 such as the one illustrated in FIG. 2A,the magnetic field 506 extends between opposite ends 502A and 502B ofthe magnet 500. In contrast with a conventional bar magnet, the magneticarray(s) described herein are formed of one or more dipole pairs ofmagnetic elements where magnetic poles of opposite polarity (N and S)are positioned adjacent one another, and the magnetic field extendsbetween adjacent opposing poles. For purposes of visualization, a dipolepair may be thought of as a conventional rod magnet that is cleaved atits center and the resulting sections brought together in a north-south(NS), side-by-side configuration.

FIGS. 2B, 2C and 2D illustrate examples of magnetic arrays 510. Each ofthe magnetic arrays in FIGS. 2B, 2C and 2D include one or more dipolepairs 510. Magnetic fields 512 corresponding to the magnetic interactionof the dipole pairs 510 are represented by curved lines. FIG. 2Billustrates a magnetic array with one dipole pair 510 with a singlecorresponding magnetic field 512, whereas FIGS. 2C and 2D show multipledipole pairs 510 arranged in series with multiple corresponding magneticfields 512. When a magnetic array includes multiple dipole pairs 510,such as illustrated in FIGS. 2C and 2D, each dipole pair 510 can be inthe same or a different orientation as that of the neighboring dipolepair 510 (e.g., [NS][NS][NS] or [NS][SN][NS]). In use, the magneticfields 512 generated by the dipole pairs 510 will induce a magneticfield in a diamagnetic material. The induced magnetic field of thediamagnetic material interacts repulsively with the applied magneticfield 512 of the dipole pairs 510 regardless of the direction of theapplied field 512 (i.e., north or south). The magnitude of the repulsiveforce between the magnetic field 512 of the dipole pairs 510 and thediamagnetic material is determined by the magnetic flux density of thecorresponding dipole pair 510 and the diamagnetic susceptibility of thediamagnetic material, in this case the skin care active. Magneticsusceptibility is a dimensionless proportionality constant thatindicates the degree of magnetization of a material in response to anapplied magnetic field. A negative magnetic susceptibility generallyindicates diamagnetism and is referred to herein as diamagneticsusceptibility. Magnetic flux density is generally greatest at themid-point 515 between the corresponding poles, and thus the strength ofthe magnetic field 512 will typically vary across the magnetic arraydepending on how the array is configured.

In practice, the substrate 580 used to form a magnetic array for useherein is typically not magnetized evenly throughout. As shown in FIG.3A, each pole 610 extends from an upper skin facing side 520 of thesubstrate 580 towards an opposing underside 522 (i.e., through thethickness of the substrate 580). A magnetic return 530 is providedbetween each adjacent pole 610 and at the second side 522 of thesubstrate 580. The magnetic return 530 is an unmagnetized area used tointegrate the magnetic fields 612 generated by each pole 610 on thatside of the substrate 580 and reduce or eliminate the magnetic flux onthe second side 522 of the substrate 580, instead diverting it towardsthe skin facing side 520. The resultant magnetic field 612 extendsoutward from the first side 520 of the substrate 580, in a directionsubstantially perpendicular to the surface of the substrate 580, and isstrongest at the mid-point 615 between adjacent opposing poles 610.

The magnetic array herein may be formed as a uni-directional array or amulti-directional array. FIG. 3C illustrates an example of auni-directional array 700. The uni-directional array 700 has north (N)and south (S) poles 710 aligned in parallel to one another in a singlelayer. Adjacent poles 710 are separated from one another by a polecenter-to-center distance P, which defines the pitch of the magneticarray 700.

FIG. 3D illustrates a portion of the magnetic field 712 generated by themagnetic array 700 of FIG. 3C in a direction W that is perpendicular tothe alignment of the poles 710. The waveform 740 illustrated in FIG. 3Dshows the magnitude of the magnetic field 712 varying regularly between+B and −B in a sinusoidal pattern, which corresponds to the differencein polarity (i.e., direction) of the magnetic field 712. The peaks 701and troughs 703 of the waveform 740 correspond to the mid-points 705between adjacent poles 710, and the inflections points 702 of thewaveform 740 correspond to the centers of the poles 710. In other words,a first maximum magnetic flux density is represented by peak 701, whichoccurs at a mid-point 705 between a first north pole 708 and an adjacentsouth pole 706, a minimum magnetic flux density represented byinflection point 702 occurs in the center of the south pole 706, and asecond maximum magnetic flux density represented by trough 703 occurs atthe mid-point 705 between the south pole 706 and a second north pole 707adjacent the south pole 706.

The amplitude of the waveform 740 is determined by the choice ofmagnetic substrate, the thickness or depth of substrate that ismagnetized and the distance from the center of a pole 710 to the edge ofthe pole 710. As the depth of magnetized area of a given substratematerial increases, the maximum amplitude of the waveform 740 increases.

The frequency of the waveform 740 is determined by the pitch P of thearray 700. A higher pitch P means that there are fewer magnetic fluxdensity “maximums” per area of substrate, and thus a lower overallmagnetic field strength for the array 700. However, a lower pitch P mayresult in respective poles 710 being packed too closely to one anotherfor any single pole 710 to reach its maximum potential magnetic fluxdensity.

FIG. 3E is an illustration of a waveform 750 representing the repulsiveforce that would be experienced by a diamagnetic material exposed to themagnetic field 712 in FIG. 3D. As shown by the waveform 750, the inducedmagnetic field of a diamagnetic material is independent of the directionof the applied magnetic field 712, and thus the change in the magnitudeof the repulsive force corresponds to the change in magnitude of theapplied magnetic field 712.

In some instances, the magnetic array herein may be formed as amulti-directional array (e.g., bi-directional array), whereby multiplelayers of parallel poles, which may be configured to play differentroles, are juxtaposed at an angle relative to one another to providemultiple magnetic fields that constructively or destructively interferewith one another. For example, a first layer of poles may determine themaximum magnetic field strength, while a second set of poles smooths outthe overall profile of the magnetic field, thereby reducing instances ofminimum magnetic flux density and ineffectual magnetic field strength.Generally, in a multi-directional array, the magnetic flux density atany one point in the magnetic array will be determined by the combinedmagnetic flux density of poles of the different layers at that point. Insome cases, this will lead to constructive interference where theresultant magnetic flux density at a point is greater than the magneticflux density at that point for each individual layer. In other cases,the combination may lead to destructive interference where the resultantmagnetic flux density at a point is less (sometimes zero) than themagnetic flux density at that point for each individual layer.

FIG. 4A illustrates an example of a bi-directional array 800A, whereinthe first and second layers of poles 802A and 804A, respectively, areformed in two separate magnetic substrates 801A and 803A, which arejuxtaposed at an angle offset from one another. The magnetic returns807A and 808A of the substrates 801A and 803A are positioned to face inthe same direction such that the magnetic field generated by both layersof poles 802A and 804A extends away from the magnetic array 800A in thesame direction. The layers of poles 802A and 804A may be identical toone another (for example, having the same pitch between adjacent polesand the same maximum field strength), or the two layers 802A and 804Amay vary in their specific parameters. Where the parameters of the twolayers 802A and 804A vary, it is preferable for the layer that isproximate the target diamagnetic material (in FIG. 4A, the second layer804A) be formed of a thinner substrate than the distal layer (in FIG.4A, the first layer 802A), otherwise the induced magnetic field of thediamagnetic material will be primarily based on the magnetic fieldstrength of the proximal layer.

FIG. 4B illustrates an example in which the first layer of poles 802Band the second layer of poles 804B are formed in the same magneticsubstrate 805. The configuration shown in FIG. 4B may be provided bymagnetizing the substrate 805 in one direction to form a first layer ofparallel aligned north and south poles 802B, and then remagnetizing thesubstrate 805 in a different direction to form a second layer 804B ofparallel aligned north and south poles to effectively form a wovenpattern of poles. In this embodiment, the depth of poles d2 in thesecond layer 604 is equal to or less than the depth d1 of poles in thefirst layer 802B. The depth d1 of the first layer 802B of poles istypically determined by the thickness T of the magnetic substrate 805.

FIG. 4C illustrates a waveform representing the three-dimensionalmagnetic field of a bidirectional magnetic array. The induced magneticfield of a diamagnetic material is independent of the direction of themagnetic field, and thus all areas of positive and negative magneticfield strength will appear as a repulsive force to a diamagneticmaterial.

The combined overall magnetic field strength of a magnetic array can bemeasured after completion of the magnetization process using any knownGaussmeter. For bi-directional magnetic arrays made of two separatesubstrates, the overall magnetic field strength can be measured firstfor the respective layers and subsequently for the combinedbi-directional magnetic array. In a bi-directional magnetic array, theoverall magnetic field strength will approximately equate to the sum ofthe field strength of the individual layers.

Dipolar pairs of the magnetic substrate may be separated from adjacentdipolar pairs by a magnetically insulating material (i.e., a materialwith a relatively low magnetic permeability). In some instances, themagnetic elements may be arranged as individual segments or sections ofmagnetized ferromagnetic materials. Additionally or alternatively, themagnetic elements may be disposed in or on a solid or semi-solidsubstrate in which the required magnetic pattern is impressed upon theferromagnetic particles or elements. The magnetic elements may be rigidelements within the applicator itself or disposed on a suitablesubstrate and joined to the applicator, for example, with an adhesive.In some instances, it may be desirable to embed the magnetic elements ina flexible matrix such as rubber or silicone and join the resultantarray to a skin facing surface of the applicator.

In a particularly suitable example of a skin care product, a magneticarray is paired with a skin care composition that includes Pal-KTTKS(SEQ ID NO: 1). Pal-KTTKS (SEQ ID NO: 1) has a diamagneticsusceptibility of approximately −519. Magnetic arrays suitable forenhancing the penetration of Pal-KTTKS (SEQ ID NO: 1) includeuni-directional and/or bi-directional arrays that exhibit enhancedpenetration of cosmetic actives with a diamagnetic susceptibility ofbetween about −400 and −600. A suitable example of a uni-directionalmagnetic array for enhancing the penetration of Pal-KTTKS (SEQ ID NO: 1)into skin is a magnetic array formed from a strontium ferrite powderimpregnated in a polyvinyl chloride PVC base. In this example, themagnetic array may have a thickness of between 0.9 and 1.3 mm (e.g.,1.0, 1.1 or 1.2 mm); a pitch of between 1.7 and 2.5 mm (e.g., 1.8, 1.9,2.0, 2.1, 2.2, 2.3 or 2.4 mm); and an overall field strength of from24.0 to 36.0 mT (e.g., about 24.5, 25, 25.5, 26, 26.5, 27, 27.5, 28,28.5, 29, 29.5, 30, 30.5, 31, 31.5, 32, 32.5, 33, 33.5, 34, 34.5, oreven about 35 mT). In a particularly suitable example of auni-directional magnetic array, the magnetic array has an overallmagnetic field strength of approximately 27 mT, a thickness of 1.1 mmand a pitch of about 2.1 mm (e.g., 12 poles per 25.4 mm).

An example of a suitable bi-directional array for enhancing thepenetration of Pal-KTTKS (SEQ ID NO: 1) into skin may have a first layerthickness of between about 0.3 and 0.9 mm (e.g., 0.4, 0.5, 0.6, 0.7 oreven 0.8 mm) and a first layer pitch of between 1.7 and 2.5 mm or about12 poles per 25.4 mm (e.g., a pitch of 1.8, 1.9, 2.0, 2.1, 2.2, 2.3 or2.4 mm), leading to a first layer magnetic field strength of between 20mT and 26 mT (e.g., 21, 22, 23, 24 or even 25 mT), especially about 23.2mT. The bi-directional array in this example may have second layerthickness of between 0.05 mm and 0.5 mm (e.g., 0.1, 0.15, 0.2, 0.25,0.3, or even 0.4 mm) and a second layer pitch of about 0.8 mm to about1.3 mm or 25 poles per 25.4 mm (e.g., a pitch of between 0.9 and 1.2 mmor between 1.0 and 1.1 mm), leading to a second layer field strength ofbetween 1 mT and 24 mT (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13,14, 15, 16, 17, 18, 19, 20, 21, 22, or 23 mT). The overall magneticfield strength of the bi-directional array may be between 14 mT and 30mT (e.g., 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28 or 29mT). The bi-directional array may have an overall magnetic fieldstrength of between about 19.0 and about 25.0 mT (e.g., 20, 21, 22, 23,or even 24 mT). Typically, in a bi-directional array, the magnetic fieldstrength of the second layer will be less than or equal to the magneticfield strength of the first layer, and/or the second layer pitch will beless than or equal to the first layer pitch. The first and second layersof the bi-directional array in this example may be formed fromuni-directional arrays that are angularly offset by between 1 and 179degrees (e.g., between 45 and 135 degrees, between 60 and 120 degrees,or even about 90 degrees).

Skin Care Composition

The skin care composition herein can help improve the appearance ofvisible and/or tactile discontinuities in mammalian skin, including finelines, wrinkles, enlarged pores, roughness, dryness, and other skintexture discontinuities, e.g., reduces or effaces the visibility of finelines, wrinkles, and other forms of uneven or rough surface textureassociated with aged or photo-damaged skin. The skin care compositionsin the present skin care product may be applied to mammalian keratinoustissue, in particular to human skin. The skin care composition may takevarious forms such as, for example, solutions, suspensions, lotions,creams, gels, toners, sticks, pencils, sprays, aerosols, ointments,cleansing liquid washes and solid bars, shampoos and hair conditioners,pastes, foams, powders, mousses, shaving creams, wipes, strips, patches,electrically-powered patches, wound dressing and adhesive bandages,hydrogels, film-forming products, facial and skin masks, cosmetics suchas foundations, eye liners, eye shadows, and the like.

The present skin care compositions contain a safe and effective amountof Pal-KTTKS (SEQ ID NO: 1), for example, Matrixyl® or Promatrixyl®brand Pal-KTTKS (SEQ ID NO: 1) (100 ppm Pal-KTTKS (SEQ ID NO: 1))available from Sederma, France. The Pal-KTTKS (SEQ ID NO: 1) may beincluded in the present skin care composition at an amount of from1×10-6% to 10% by weight of the composition (e.g., 1×10-6% to 0.1%, evenfrom 1×10-5% to 0.01%). In embodiments wherein Matrixyl® or Promatrixyl®is used, the resulting composition preferably contains from 0.01% to50%, by weight of the resulting composition, of Matrixyl® orPromatrixyl® (e.g., from 0.05% to 20%, or from 0.1% to 10%). The presentskin care compositions may include additional optional ingredients knownfor safe use in skin care compositions (e.g., emollients, humectants,vitamins; peptides; and sugar amines, sunscreen actives (or sunscreenagents), ultraviolet light absorbers, colorants, surfactants,film-forming compositions, and rheology modifiers). Some non-limitingexamples of optional ingredients for use in the present compositions aredisclosed in U.S. Publication No. US2008/0206373, filed by Millikin, etal., on Feb. 28, 2008.

Methods of Use

The skin care product disclosed herein may be used to apply a skin carecomposition to one or more skin surfaces as part of a user's dailyroutine. Additionally or alternatively, the cosmetic compositions hereinmay be used on an “as needed” basis. For example, the cosmeticcomposition may be applied to a facial skin care surface in need oftreatment. The facial skin surface may include one or more of the cheek,forehead, and peri-orbital areas of the face. In some examples, one ormore of these skin surfaces may be identified as needing treatment whensigns of skin aging are observed on the target skin surface. In theseinstances, the present composition may be applied to the target skinsurface. For example, the cosmetic composition can also be applied tothe facial skin surface at least once per day, twice per day, or threetimes per day for a period of 7, 14, 21, or 28 days or more. In anotherexample, the cosmetic composition may be applied to a different skinsurface or applied to facial skin and one or more different skinsurfaces.

Example 1—Pal-KTTKS (SEQ ID NO: 1) Ex Vivo Skin Penetration Study

An ex vivo skin penetration study was conducted to compare the abilityof different magnetic arrays to enhance penetration of Pal-KTTKS (SEQ IDNO: 1) into the epidermis of human skin. The dermis and epidermis ofhuman skin samples obtained from donors aged 60-65 years were heatseparated and the dermis discarded. 20 μL of a Pal-KTTKS (SEQ ID NO: 1)containing composition (400 μg/ml in 50:50 PG:PB at pH 4) was placed onhuman epidermis in Franz cell. Different magnetic arrays were positionedapproximately 1.0 mm above the epidermis samples and moved over thesamples at the speed a user might move a cosmetic applicator whenapplying a skin care product (e.g., about 20-25 cm/sec). Samples weretaken and measured at 0, 1, 2, 4, 6, 8, 24 hours. Of the arrays tested,two particular arrays, which are set forth in Table 1 below,demonstrated the best penetration enhancement of Pal-KTTKS (SEQ ID NO:1). For the bi-directional arrays herein, the “1st layer” refers to thelayer closest to the skin-contacting surface of the applicator, and the“2^(nd) layer” refers to the layer disposed on the side of the 1^(st)layer opposite the side closest to the skin-contacting surface.

TABLE 1 Magnetic Field Angle Array Thickness (mm) Pitch (mm) Poles per25.4 cm Strength (mT) offset 1 Uni-directional 1.1 2.13 12 27 n/a 2Bi-directional 1st layer: 0.6 1st layer: 2.13 1st layer: 12 1st layer:27 90° 2^(nd) layer: 0.2 2^(nd) layer: 1.06 2^(nd) layer: 25 2^(nd)layer: ~4 Overall: 21

Example 2—Pal-KTTKS (SEQ ID NO: 1) In Vivo Skin Penetration Study #1

An in vivo skin penetration study was conducted to establish the effectof using a skin care product of the present invention by applying a skincare composition comprising Pal-KTTKS (SEQ ID NO: 1) with an applicatorcomprising a magnetic array. The study compared the penetration of thePal-KTTKS (SEQ ID NO: 1) in combination with a variety of magneticarrays (active application) to the penetration of Pal-KTTKS (SEQ IDNO: 1) applied with a finger (passive application). Penetration ofPal-KTTKS (SEQ ID NO: 1) in this example is determined according to theTape Stripping method. In this example, the level of Pal-KTTKS (SEQ IDNO: 1) present in the extract from each tape strip was measured usingHPLC and the results normalized to the protein level measured on thetape strip. While passive delivery is accomplished using a finger, it isto be appreciated that passive delivery may also be accomplished usingan applicator or other device that does not include a magnetic arraytailored to enhance penetration of Pal-KTTKS (SEQ ID NO: 1).

Tape Stripping Method

This method provides a suitable means of measuring the amount of skincare active present in skin, and comparing active versus passiveapplication of the skin care active. Two identical rectangular areas of15 cm² are marked on the volar forearms of volunteers. A measured dose(approximately 30 mg) of the Pal-KTTKS (SEQ ID NO: 1) formulation isapplied to the delineated areas using a screw actuated syringe. Activeapplication is carried out on one of the delineated areas using thethree-quarter profile of a purpose made applicator (e.g., an applicatorpresenting one of the magnetic arrays set forth in Table 2). Passiveapplication is accomplished on the other delineated area using the tipof a finger in a sweeping motion identical to that of the activeapplication. The formulation is spread evenly across the entiredelineated region using a sweeping motion with a fixed speed ofapproximately 23 cm/s to mimic typical. The application period is 30seconds during which time visual inspection is used to ensure evendistribution and absorption of the formulation by skin. The applicationarea is then left uncovered for a further 30 minutes to ensure completeabsorption. Tape strip samples may be collected and/or analyzedimmediately after the complete absorption is ensured or after a waitingperiod (e.g., after multiple applications of the formulation overmultiple hours or days).

The tape stripping procedure is carried out using 10 commercial pre-cut22.1 mm tape stripping adhesive discs (e.g., D-SQUAME brand tape strips,available from Cuderm Corporation, or equivalent) with an adhesive areaof 3.8 cm². The 10 tape strips are applied sequentially to the samesampling site, which ideally enables each tape strip to obtain a samplefrom deeper within the stratum corneum than the tape strip that precededit. A 22.1 mm diameter circular region is marked at the center of theapplication area. A tape stripping adhesive disc is placed over themarked area and even pressure applied using, for example, a neopreneroller, rolled ten times over the adhesive disc. The adhesive disc isremoved from the skin surface in a single pulling motion using manualtweezers. To ensure even removal of the skin sample, subsequent discsare removed in a “north, south, east and west” orientation, which iswithin the skill of the ordinary artisan. Each adhesive disc isnon-destructively analyzed for protein content using a suitableinstrument (e.g., SquameScan™ 850 instrument commercially available fromHeiland Electronics Wetzlar, Germany, or equivalent). The adhesive discis then immediately placed into a glass vial containing extractionsolvent in preparation for subsequent analysis. Solvent extractions areconducted on each tape strip using conventional extraction methods,which are well known to those of ordinary skill in the art, andmeasuring the amount of Pal-KTTKS (SEQ ID NO: 1) present in the extract,for example, by high performance liquid chromatography (“HPLC”) and/ormass spectrometry.

The procedure is repeated for the remaining nine strips. An additionalstrip is obtained from outside the area of application of the skin careformulation to serve as a blank sample. The amount of active isnormalized to the amount of protein measured.

Delivery of the Pal-KTTKS (SEQ ID NO: 1) is said to be enhanced when aratio of active to passive delivery, as determined according to the TapeStripping method, is greater than 1. In other words, if activeapplication of the skin care composition yields more Pal-KTTKS (SEQ IDNO: 1) as compared to the corresponding passive application, thendelivery is said to be enhanced. The active and corresponding passiveapplication values may be compared individually (e.g., single tape stripcomparison) or as group of two or more values (e.g., the sum totaland/or average values of tape strips 8, 9, and 10 for the active andpassive applications may be compared to determine if penetration wasenhanced). The tailored magnetic arrays herein enhance delivery ofPal-KTTKS (SEQ ID NO: 1). Enhanced delivery may be from 1.5× to 20× (2×,2.5, 3×, 3.5×, 4×, 4.5×, 5×, 5.5×, 6×, 6.5×, 7×, 7.5×, 8×, 8.5×, 9×,9.5× or even 10× or more).

Table 2 shows the magnetic arrays used in the tests described in moredetail below. The magnetic arrays shown in Table 2 provide a variety ofconfigurations to compare how different magnetic arrays enhancepenetration of the Pal-KTTKS (SEQ ID NO: 1) in vivo. The magnetic arraysin Table 2 vary in thickness, pitch, and/or magnetic field strength. Thetwo layers of magnetic arrays in the bi-directional arrays shown inTable 2 (i.e., arrays #8 and #9) are angularly offset by 90 degrees.

TABLE 2 Poles Magnetic Field Array Thickness (mm) Pitch (mm) per 25.4 cmStrength (mT) 1 Uni-directional 0.2 2.13 12  9.8 2 Uni-directional 0.42.13 12 16.3 3 Uni-directional 0.6 2.13 12 23.2 4 Uni-directional 1.12.13 12 27 5 Uni-directional 1.1 3.18  8 4-10 6 Uni-directional 1.1 1.4917 19.8 7 Uni-directional 1.1 1.0 25 11.5 8 Bi-directional 1st layer:0.6 1st layer: 2.13 1st layer: 12 1st layer: 23.2 2^(nd) layer: 0.22^(nd) layer: 1.49 2^(nd) layer: 17 2^(nd) layer: 9.8 9 Bi-directional1st layer: 0.6 1st layer: 2.13 1st layer: 12 1st layer: 23.2 2^(nd)layer: 0.2 2^(nd) layer: 1.06 2^(nd) layer: 25 2^(nd) layer: 4-10

Table 3 shows the amount of Pal-KTTKS (SEQ ID NO: 1) (ng/stripnormalized for protein content) measured on ten tape strip samples froma first test subject after active application of a Pal-KTTKS (SEQ IDNO: 1) formulation using several of the arrays in Table 2. The arraynumber shown in Table 3 corresponds to the array of the same number inTable 2. Table 4 shows the average amounts (ng/strip) of Pal-KTTKS (SEQID NO: 1) measured on ten tape strip samples from a first test subjectafter passive application of the same Pal-KTTKS (SEQ ID NO: 1)formulation using a finger. The array number shown in Table 4 indicateswhich array in Table 3 the passive application is being compared to.Tape stripping and analysis of the resulting samples was conductedaccording to the Tape Stripping method, and commenced at the conclusionof four days and 8 applications of the Pal-KTTKS (SEQ ID NO: 1)formulation (2 applications per day). Array #4 was tested twice.

TABLE 3 Active Application Array strip 1 2 3 4 4 5 6 8 9 1 56.96 46.9261.09 35.01 45.77 33.38 59.87 39.68 73.27 2 49.66 53.18 40.67 46.4121.58 23.71 54.00 37.11 57.70 3 46.77 29.37 43.64 58.65 35.26 26.8536.23 24.63 60.39 4 41.88 66.20 22.16 53.42 25.62 28.25 41.38 21.7159.04 5 38.78 53.17 28.93 43.64 28.78 23.41 34.55 23.23 51.72 6 30.8036.55 35.18 50.02 41.63 30.99 27.18 22.53 44.43 7 34.10 51.40 34.4561.19 47.01 29.47 27.17 21.41 35.56 8 23.34 41.22 44.32 48.91 24.7238.99 55.02 24.62 53.12 9 37.21 51.97 33.60 38.30 33.67 30.46 36.8723.43 56.29 10 30.72 50.00 30.15 33.82 32.64 23.53 27.33 29.50 44.61

TABLE 4 Passive Application Corresponding Array 1 2 3 4 4 5 6 8 9 149.32 49.32 49.32 16.35 41.17 16.35 16.35 41.17 41.17 2 40.95 40.9540.95 22.39 34.37 22.39 22.39 34.37 34.37 3 27.86 27.86 27.86 35.0722.33 35.07 35.07 22.33 22.33 4 23.05 23.05 23.05 22.48 13.19 22.4822.48 13.19 13.19 5 37.15 37.15 37.15 23.37 12.53 23.37 23.37 12.5312.53 6 29.58 29.58 29.58 23.13 11.02 23.13 23.13 11.02 11.02 7 25.5625.56 25.56 19.08 11.80 19.08 19.08 11.80 11.80 8 27.42 27.42 27.4215.90 14.32 15.90 15.90 14.32 14.32 9 5.59 5.59 5.59 15.63 7.24 15.6315.63 7.24 7.24 10 0.04 0.04 0.04 0.47 0.09 0.47 0.47 0.09 0.09

Table 5 shows the amount (ng/strip) of Pal-KTTKS (SEQ ID NO: 1) measuredon ten tape strip samples from a second test subject after activeapplication of a Pal-KTTKS (SEQ ID NO: 1) formulation using several ofthe arrays in Table 2. The array number shown in Table 5 corresponds tothe array of the same number in Table 2. Table 6 shows the averageamounts (ng/strip) of Pal-KTTKS (SEQ ID NO: 1) measured on ten tapestrip samples from a first test subject after passive application of thesame Pal-KTTKS (SEQ ID NO: 1) formulation using a finger. The arraynumber shown in Table 6 indicates which array in Table 5 the passiveapplication is being compared to. Active and passive application of thePal-KTTKS (SEQ ID NO: 1) formulation, and tape stripping and analysis ofthe resulting samples was conducted according to the Tape Strippingmethod, and commenced at the conclusion of four days and 8 applicationsof the Pal-KTTKS (SEQ ID NO: 1) formulation (2 applications per day).Array #4 and Array #7 were each tested twice.

TABLE 5 Active Application for Test Subject #2 Array 1 2 3 4 4 5 6 7 7 91 76.41 148.76 187.34 143.27 73.85 80.05 66.63 147.51 49.89 274.82 254.30 96.01 125.89 51.26 42.10 35.19 37.58 82.13 32.67 196.94 3 52.2686.48 110.76 40.60 29.31 49.58 78.62 65.63 15.36 120.05 4 48.35 54.3078.75 37.47 22.68 30.88 73.91 49.00 25.87 123.15 5 57.60 61.43 88.6237.70 21.36 33.85 47.22 44.25 24.98 68.88 6 37.03 79.21 84.18 22.6526.01 29.49 47.82 36.69 20.32 25.76 7 41.96 64.48 74.48 61.16 26.0429.59 22.08 27.44 13.69 5.39 8 37.39 52.42 71.79 47.56 25.65 42.94 33.2317.97 18.69 53.82 9 48.08 46.36 55.40 43.19 20.84 34.00 25.30 36.5714.47 5.32 10 50.53 58.95 67.46 24.47 20.63 34.38 12.89 17.97 15.35 5.12

TABLE 6 Passive Application for Test Subject #2 Corresponding Arraystrip 1 2 3 4 4 5 6 7 7 9 1 79.15 79.00 79.00 54.19 65.62 79.15 79.1565.62 54.19 91.46 2 25.05 49.04 49.04 42.07 20.19 25.05 25.05 20.1942.07 5.91 3 1.57 32.82 32.82 27.06 0.51 1.57 1.57 0.51 27.06 16.15 46.18 32.53 32.53 16.96 7.33 6.18 6.18 7.33 16.96 8.23 5 0.17 38.10 38.1020.57 11.52 0.17 0.17 11.52 20.57 5.39 6 12.08 35.30 35.30 15.92 6.3912.08 12.08 6.39 15.92 11.76 7 12.57 40.89 40.89 10.45 5.21 12.57 12.575.21 10.45 22.47 8 14.11 39.07 39.07 4.99 6.57 14.11 14.11 6.57 4.995.59 9 9.61 29.03 29.03 11.68 4.74 9.61 9.61 4.74 11.68 5.42 10 12.8618.51 18.51 8.84 7.45 12.86 12.86 7.45 8.84 5.22

Table 7 shows the amount (ng/strip) of Pal-KTTKS (SEQ ID NO: 1) measuredon ten tape strip samples from a third test subject after activeapplication of a Pal-KTTKS (SEQ ID NO: 1) formulation using several ofthe arrays in Table 2. The array number shown in Table 7 corresponds tothe array of the same number in Table 2. Table 8 shows the averageamounts (ng/strip) of Pal-KTTKS (SEQ ID NO: 1) measured on ten tapestrip samples from a first test subject after passive application of thesame Pal-KTTKS (SEQ ID NO: 1) formulation using a finger. The arraynumber shown in Table 8 indicates which array in Table 7 the passiveapplication is being compared to. Active and passive application of thePal-KTTKS (SEQ ID NO: 1) formulation, and tape stripping and analysis ofthe resulting samples was conducted according to the Tape Strippingmethod, and commenced at the conclusion of four days and 8 applicationsof the Pal-KTTKS (SEQ ID NO: 1) formulation (2 applications per day).Array #4 was tested twice.

TABLE 7 Active Application for Test Subject #3 Array strip 1 2 3 4 4 5 67 8 9 1 180.96 87.78 41.15 101.60 46.93 30.35 47.37 209.62 46.42 59.76 2158.86 72.34 56.25 80.32 27.46 619.23 46.55 172.48 44.20 62.74 3 149.3173.97 60.85 90.50 27.44 322.26 72.34 187.98 41.37 55.25 4 166.70 65.5255.34 82.01 24.76 195.47 66.29 185.07 46.80 53.81 5 182.66 69.46 48.9784.48 24.36 25.48 23.87 172.13 35.94 45.48 6 159.00 82.45 39.54 98.8223.21 4.78 41.92 187.40 34.93 44.70 7 140.35 63.67 55.15 83.27 25.025.10 30.77 176.71 34.48 38.11 8 190.78 74.85 52.95 85.83 21.54 147.6835.00 142.37 26.94 46.29 9 134.01 71.91 46.83 85.16 16.63 30.04 24.48171.43 13.01 36.70 10 152.16 74.08 30.52 75.04 15.28 41.43 45.18 178.8710.11 39.72

TABLE 8 Passive Application for Test Subject #3 Corresponding Arraystrip 1 2 3 4 4 5 6 7 8 9 1 188.13 49.17 31.64 49.17 32.55 179.06 31.64188.13 32.55 32.55 2 157.66 39.50 28.92 39.50 28.14 44.86 28.92 157.6628.14 28.14 3 161.29 38.06 23.16 38.06 27.78 116.86 23.16 161.29 27.7827.78 4 143.20 37.52 20.62 37.52 32.27 140.42 20.62 143.20 32.27 32.27 5102.85 19.72 26.14 19.72 27.05 103.88 26.14 102.85 27.05 27.05 6 112.4914.11 37.90 14.11 26.40 53.64 37.90 112.49 26.40 26.40 7 122.71 39.0336.62 39.03 23.07 13.11 36.62 122.71 23.07 23.07 8 120.11 36.50 34.5436.50 22.06 79.01 34.54 120.11 22.06 22.06 9 132.60 44.38 28.51 44.3815.64 18.60 28.51 132.60 15.64 15.64 10 145.23 55.49 27.32 55.49 14.7561.48 27.32 145.23 14.75 14.75

Magnetic array #9 demonstrated better penetration enhancement than someof the other magnetic arrays tested. The average Pal-KTTKS (SEQ IDNO: 1) actively and passively delivered to the three test subjects isplotted in the graph shown in FIG. 5. Table 9 shows the combined amountof Pal-KTTKS (SEQ ID NO: 1) measured on tape strips 2, 3 and 4; 5, 6 and7; and 8, 9 and 10 for active application with bi-directional magneticarray #9 (as shown in Table 2) and the corresponding passiveapplication. The combined amounts were averaged for test subject andstrip. As shown in Table 9, active application resulted in significantenhanced delivery of Pal-KTTKS (SEQ ID NO: 1) compared to passiveapplication.

TABLE 9 Magnetic Array #9 combined Subject strips 1 2 3 average ActiveApplication s2-s4 177.13 440.14 171.79 263.02 s5-s7 131.72 100.02 128.29120.01 s8-s10 154.03 64.27 122.70 113.67 Mean 154.29 201.48 140.93165.57 Passive Application s2-s4 69.89 30.29 88.18 62.79 s5-s7 35.3539.62 76.52 50.50 s8-s10 21.64 16.23 52.45 30.11 Mean 42.29 28.71 72.3947.80

Table 10 provides a statistical comparison of active delivery to passivedelivery based on the average values shown in the last column of Table9.

TABLE 10 Enhancement strips p value (active/passive) s2-s4 0.156 4.19S5-s7 0.0135 2.38 S8-s10 0.0437 3.78

Magnetic array #4 also demonstrated better penetration enhancement thansome of the other magnetic arrays tested. The average Pal-KTTKS (SEQ IDNO: 1) actively and passively delivered to the three test subjects isplotted in the graph shown in FIG. 6. Table 11 shows the combined amountof Pal-KTTKS (SEQ ID NO: 1) measured on tape strips 2, 3 and 4; 5, 6 and7; and 8, 9 and 10 for active application with uni-directional magneticarray #4 (as shown in Table 2) and the corresponding passiveapplication. The combined amounts were averaged for test subject andstrip. As shown in Table 11, active application resulted in significantenhanced delivery of Pal-KTTKS (SEQ ID NO: 1) compared to passiveapplication.

TABLE 11 Magnetic Array # 4 Subject combined strips 1 2 3 Average ActiveApplication s2-s4 158.48 82.45 129.33 94.10 79.66 108.81 s5-s7 154.85117.42 121.51 73.41 72.59 107.95 s8-s10 121.04 91.03 115.22 67.12 53.4589.57 Mean 144.79 96.97 122.02 78.21 68.57 102.11 Passive Applications2-s4 79.94 69.89 86.09 28.02 88.18 70.42 s5-s7 65.58 35.35 46.95 23.1176.52 49.50 s8-s10 32.01 21.64 25.51 18.76 52.45 30.08 Mean 59.18 42.2952.85 23.30 72.39 50.00

Table 12 provides a statistical comparison of active delivery to passivedelivery based on the average values shown in the last column of Table11.

TABLE 12 Enhancement strips p value (active/passive) s2-s4 0.0760 1.54S5-s7 0.0132 2.18 S8-s10 0.0034 2.98

Example 3—Pal-KTTKS (SEQ ID NO: 1) In Vivo Skin Penetration Study #2

This in vivo skin penetration study compares the penetration ofPal-KTTKS (SEQ ID NO: 1) into skin when a Pal-KTTKS (SEQ ID NO:1)-containing composition is applied with a magnetic applicator (activeapplication) versus application with a non-magnetic applicator (passiveapplication). In this example, 5 test subjects (A to E in Tables 13 and14) were selected. 18 mg of a composition containing Pal-KTTKS (SEQ IDNO: 1) (Olay® Deep Wrinkle Treatment® brand skin cream available fromthe Procter & Gamble Company, Cincinnati, Ohio) was applied to two 3cm×3 cm test sites on the inner forearms of each test subject using theapplicator illustrated in FIG. 1C. The applicator used for activeapplication included Array #8 from Table 2. The applicator used forpassive application was the same as the one used for active applicationexcept without the magnetic array. Each forearm included an activeapplication test site and a passive application site for a total of 10active test sites and 10 passive sites. The application time was 30seconds with a speed of motion of approximately 3 cm per second,equating to a gentle rubbing action. Application of the composition wasfollowed by a 30 minute absorption period. The results of the passiveand active application are shown in Tables 13 and 14 below. Penetrationof Pal-KTTKS (SEQ ID NO: 1) was determined according to the TapeStripping Method. The level of Pal-KTTKS (SEQ ID NO: 1) recovered fromeach tape strip was measured using HPLC and normalized to the totalprotein level measured on the tape strip.

Tables 13 and 14 show the amount of Pal-KTTKS (SEQ ID NO: 1) recoveredfrom each tape strip. Table 13 shows the results of applying thecomposition using a non-magnetic applicator, and Table 14 shows theresults of applying the composition with a magnetic applicatorconfigured to enhance penetration of Pal-KTTKS (SEQ ID NO: 1). Theaverage value across all test sites is shown in the second to last cellof the row. The standard error of the mean (SEM) is shown in the lastcolumn of Tables 13 and 14. The SEM is calculated by dividing thestandard deviation by the square root of the number of test sites. Theactive versus passive application results from Tables 13 and 14 aregraphically illustrated in FIG. 7.

TABLE 13 Passive Application Test Test Test Test Test Subject A SubjectB Subject C Subject D Subject E Site 1 Site 2 Site 1 Site 2 Site 1 Site2 Site 1 Site 2 Site 1 Site 2 Avg SEM 1 11.87 1.77 8.98 0.00 15.35 11.186.90 15.05 8.02 6.31 8.54 1.61 2 7.83 0.00 5.94 5.32 4.08 9.21 4.51 5.441.66 3.51 4.75 0.85 3 6.62 0.00 2.46 3.17 2.68 7.90 1.44 2.37 1.77 2.163.06 0.76 4 7.56 2.45 1.93 1.08 1.83 8.33 1.22 0.00 1.27 1.76 2.74 0.895 7.02 0.00 1.39 1.04 0.00 7.60 1.29 0.00 0.80 1.09 2.02 0.90 6 6.460.00 0.86 0.00 0.00 7.45 0.00 0.00 0.39 0.65 1.58 0.90 7 6.98 0.00 0.000.00 3.40 7.75 2.06 0.00 0.52 0.58 2.13 0.94 8 6.75 0.00 0.00 0.00 0.006.68 0.00 0.00 0.00 0.00 1.34 0.90 9 6.60 0.00 0.00 0.00 2.16 7.62 0.000.00 0.00 0.00 1.64 0.94 10  6.58 0.00 0.00 0.00 0.00 6.32 0.00 0.000.00 0.00 1.29 0.86 Sum 2-10 62.40 2.45 12.58 10.61 14.16 68.87 10.537.81 6.41 9.74 20.55 7.60 Sum 6-10 40.39 0.00 2.25 1.04 5.56 43.44 3.350.00 1.72 2.31 10.01 5.35

TABLE 14 Active Application Test Test Test Test Test Subject A Subject BSubject C Subject D Subject E Site 1 Site 2 Site 1 Site 2 Site 1 Site 2Site 1 Site 2 Site 1 Site 2 Avg SEM 1 15.33 2.41 15.52 24.11 8.97 15.206.49 13.55 12.28 13.73 12.76 1.86 2 10.60 8.89 10.74 10.58 4.67 15.664.28 5.70 5.94 7.16 8.42 1.12 3 9.50 8.28 5.95 6.45 4.17 11.45 2.20 2.783.85 4.27 5.89 0.96 4 9.52 5.95 4.62 2.86 3.40 9.11 2.36 1.80 6.52 3.514.96 0.86 5 9.54 4.20 5.81 5.35 2.53 11.04 1.78 1.87 5.05 3.61 5.08 0.986 9.75 3.74 4.53 0.95 2.72 9.58 2.42 2.01 5.05 3.97 4.47 0.95 7 9.732.37 3.71 3.22 2.25 10.34 2.01 1.45 2.71 1.43 3.92 1.04 8 8.16 3.18 3.384.89 3.20 7.92 1.59 0.00 0.53 1.88 3.47 0.89 9 8.07 2.51 1.99 2.55 3.437.87 0.99 1.41 1.07 0.95 3.08 0.85 10  8.56 1.29 1.94 0.00 5.27 7.910.47 1.28 0.45 0.00 2.72 1.04 Sum 2-10 83.43 40.40 42.67 36.84 31.6490.87 18.10 18.31 31.17 26.78 42.02 7.97 Sum 6-10 53.81 17.29 21.3616.95 19.40 54.66 9.26 8.02 14.86 11.84 22.74 5.42

Table 15 compares the results of active application versus passiveapplication based on the additive amounts of Pal-KTTKS (SEQ ID NO: 1)recovered from tape strips 2 to 10 and 6 to 10. The enhancement valuesshown in Table 15 are calculated by dividing the active value from Table14 by the passive value from Table 13. The average shown in the lastcolumn of Table 15 is calculated by averaging the enhancement values ofall the test sites. In instances where the passive value from Table 13was zero, resulting in a divide-by-zero situation, the enhancement valueis not included for purposes of the average. The p-value is calculatedusing a paired t-test. As shown in Table 15, active application of thecomposition delivered an average of 4× as much Pal-KTTKS (SEQ ID NO: 1)into the skin compared to passive application according to tape strips2-10, and over 6× as much when according to tape strips 6-10. Thissuggests that the specific magnetic applicator used in this example candrive Pal-KTTKS (SEQ ID NO: 1) deeper into the skin where it can providean improved skin care benefit.

TABLE 15 Comparison of Active v. Passive Application Test Test Test TestTest Subject A Subject B Subject C Subject D Subject E Site 1 Site 2Site 1 Site 2 Site 1 Site 2 Site 1 Site 2 Site 1 Site 2 Avg P-valueEnhancement 1.34 16.52 3.39 3.47 2.23 1.32 1.72 2.35 4.86 2.75 4.003.533 × 10⁻⁵ value Strips 2-10 Enhancement 1.33 — 18.16 — 3.03 1.22 3.63— 10.70 6.73 6.40 4.526 × 10⁻⁶ value Strips 6-10

Example 4—Coefficient of Friction

Coefficient of Friction Method

This method provides a means to determine the coefficient of friction ofmaterial surfaces herein. Wet coefficient of friction refers to thecoefficient of friction measured on a surface on which a skin carecomposition is present. Dry coefficient of friction refers to thecoefficient of friction measured on a surface on which a skin carecomposition is not present.

Coefficient of friction is the ratio of the force of friction betweentwo bodies and the force pressing them together. The instrument used todetermine the coefficient of friction is a Bruker® UMT-2 tribometer orequivalent. A purple nitrile glove is used as one of the two materialsin the test. The other material used in the test is the test surface(e.g., skin contacting surface of the applicator or cover). The purplenitrile glove material is placed over the probe of the tribometer. Thetest surface to be measured is placed in contact with thenitrile-covered probe of the instrument, and the force is measuredaccording to the manufacturer's operating instructions for theinstrument.

FIG. 8 illustrates the system 900 used to measure coefficient offriction in this example. As shown in FIG. 8, a probe 902 covered withpurple nitrile glove material is contacted with the skin-contactingsurface 920 of an applicator 910. In this example, the cover has beenremoved from the applicator 910 and the magnetic array provides theskin-contacting surface 920. The skin-contacting surface of the cover(not shown) was also measured. Both the applicator surface 920 and thecover were tested with and without a skin care composition (Olay® DeepWrinkle Treatment® brand skin cream available from the Procter & GambleCo., Ohio). For measuring wet coefficient of friction, 0.1 g of the skincare composition was spread over the test surface. The rate of the probewas set to 1 mm/sec with a force of 100 grams.

Each leg of the test was repeated three times. The coefficient offriction results are shown in Table 16 below.

TABLE 16 Coefficient of Friction Surface 1 2 3 Avg. Applicator surface(dry) 1.90 1.97 1.86 1.91 Applicator surface (wet) 0.45 0.62 0.45 0.50Cover surface (dry) 0.77 0.96 1.09 0.94 Cover surface (wet) 0.06 0.060.06 0.06

The dimensions and values disclosed herein are not to be understood asbeing strictly limited to the exact numerical values recited. Instead,unless otherwise specified, each such dimension is intended to mean boththe recited value and a functionally equivalent range surrounding thatvalue. For example, a dimension disclosed as “40 mm” is intended to mean“about 40 mm.”

All documents cited in the Detailed Description of the Invention are, inrelevant part, incorporated herein by reference; the citation of anydocument is not to be construed as an admission that it is prior artwith respect to the present invention. To the extent that any meaning ordefinition of a term in this document conflicts with any meaning ordefinition of the same term in a document incorporated by reference, themeaning or definition assigned to that term in this document shallgovern.

While particular embodiments of the present invention have beenillustrated and described, it would be obvious to those skilled in theart that various other changes and modifications can be made withoutdeparting from the spirit and scope of the invention. It is thereforeintended to cover in the appended claims all such changes andmodifications that are within the scope of this invention.

What is claimed is:
 1. A cosmetic skin care product, comprising: a. anapplicator comprising a substrate with a magnetic array embeddedtherein, the magnetic array comprising a first layer of dipole pairs ofalternating magnetic poles with a pitch of between 1.7 and 2.5 and amagnetic field strength of between about 24.0 and 36.0 mT, and a secondlayer of dipole pairs of alternating magnetic poles having a thicknessof between about 0.05 mm and about 0.5 mm, wherein the magnetizedsubstrate enhances penetration of pal-KTTKS (SEQ ID NO: 1) into skin;and b. a skin care composition comprising Pal-KTTKS (SEQ ID NO: 1) and adermatologically acceptable carrier.
 2. The skin care product of claim1, wherein the first layer has a thickness of between 0.8 and 1.2 mm. 3.The skin care product of claim 1, wherein the magnetic array enhancesdelivery of the Pal-KTTKS (SEQ ID NO: 1) by at least 1.5 times betterthan an applicator that does not include the magnetic array.
 4. The skincare product of claim 3, wherein the magnetic array enhances delivery ofthe Pal-KTTKS (SEQ ID NO: 1) as measured in tape strips 2 to 10according to the Tape Strip Method.
 5. The skin care product of claim 1,wherein the substrate further comprises a ferromagnetic material.
 6. Theskin care product of claim 5, wherein the ferromagnetic material isselected from iron, iron containing materials, cobalt, cobalt containingmaterials, strontium, strontium containing materials, barium, bariumcontaining materials, nickel, nickel containing materials, alloys andoxides of these and combinations thereof.
 7. The skin care product ofclaim 1, wherein the substrate comprises boron, carbon, silicon,phosphorous, aluminum, neodymium, samarium or a combination of these. 8.The skin care product of claim 1, wherein the magnetic substrateincludes a skin facing side and a distal side opposed thereto, and amagnetic return is provided at the distal side.
 9. The skin care productof claim 1, wherein the applicator further comprises a cover that coversa skin facing surface of the applicator.
 10. The skin care product ofclaim 9, wherein the cover comprises a surface having a dry coefficientof friction that is at least 10% less than the skin facing surface ofthe applicator according to the Friction Test.
 11. The skin care productof claim 1, wherein the magnetic array includes a second layer of atleast one dipole pair of alternating magnetic poles, and wherein thesecond layer has a pitch and a magnetic field strength that are bothless than or equal to the pitch and magnetic field strength of the firstlayer.
 12. The skin care product of claim 11, wherein the second layerhas a pitch of between 0.8 and 1.3.
 13. The skin care product of claim11, wherein the second layer has a magnetic field strength of betweenabout 1 and 20 mT.
 14. The skin care product of claim 11, wherein thefirst layer is angularly offset from the second layer to form abi-directional magnetic array.
 15. The skin care product of claim 14,wherein the first and second layers are angularly offset by about 90degrees.
 16. The skin care product of claim 1, wherein the applicatorand the skin care composition are packaged in separate packages, whichare joined to one another, and at least one of the applicator packageand the skin care composition package includes indicia that non-verballycommunicate to a user that the magnetic array enhances penetration ofthe Pal-KTTKS (SEQ ID NO: 1).